高良姜素调节AMPK/SIRT1/PGC-1α信号通路对高氧致早产大鼠肺损伤的影响

Effect of galangin on hyperoxia-induced lung injury in premature rats by regulating the AMPK/SIRT1/PGC-1αsignaling pathway

目的探讨高良姜素(Ga)对高氧致早产大鼠肺损伤及腺苷酸活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ辅活化因子1α(PGC-1α)信号通路的影响。方法建立高氧致早产大鼠肺损伤模型,将大鼠分为对照组(Control组)、模型组(Model组)、Ga低剂量组(Ga-L组)、Ga高剂量组(Ga-H组)、Ga-H+AMPK抑制剂Dorsomorphin组(Ga-H+Dors组);检测大鼠肺湿重/干重比值;H-E染色观察肺组织病理变化;ELISA检测支气管肺泡灌洗液(BALF)肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)水平;试剂盒检测超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽(GSH)水平;TUNEL染色检测肺组织细胞凋亡情况;Western blot检测Bcl-2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)、AMPK、SIRT1、PGC-1α蛋白表达。结果与Control组相比,Model组早产大鼠肺湿重/干重比值、TNF-α、IL-6、MDA、细胞凋亡率、Bax水平升高,SOD、GSH、Bcl-2、p-AMPK/AMPK、SIRT1、PGC-1α水平降低(P<0.05);与Model组相比,Ga-L、Ga-H组早产大鼠肺湿重/干重比值、TNF-α、IL-6、MDA、细胞凋亡率、Bax水平降低,SOD、GSH、Bcl-2、p-AMPK/AMPK、SIRT1、PGC-1α水平升高(P<0.05);Dorsomorphin减弱了Ga-H对高氧致早产大鼠肺损伤的改善作用。结论Ga可能通过激活AMPK/SIRT1/PGC-1α通路,抑制炎症、氧化应激和细胞凋亡,减轻高氧致早产大鼠的肺损伤。

Objective To investigate the effect of galangin(Ga)on hyperoxia-induced lung injury and adenylate activated protein kinase(AMPK)/silent information regulator factor 1(SIRT1)/peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α)pathway in premature rats.Methods The hyperoxia induced lung injury model of premature rats was established.The rats were divided into Control group,Model group,low and high dose Ga groups(Ga-L group,Ga-H group),and Ga-H+AMPK inhibitor Dorsomorphin group(Ga-H+Dors group);the wet to dry weight ratio of rat lungs was detected;H-E staining was used to observe pathological changes in lung tissue.ELISA was used to detect tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in bronchoalveolar lavage fluid(BALF).The kits were used to detect levels of superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione(GSH).TUNEL staining was used to detect apoptosis in lung tissue cells.Western blot was used to detect the expression of BCL2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),AMPK,SIRT1,and PGC-1αproteins.Results Compared with Control group,the ratio of lung wet weight to dry weight,TNF-α,IL-6,MDA,cell apoptosis rate,and the level of Bax in Model group were increased,the levels of SOD,GSH,Bcl-2,p-AMPK/AMPK,SIRT1,and PGC-1αwere reduced(P<0.05);compared with Model group,the ratio of lung wet weight to dry weight,TNF-α,IL-6,MDA,cell apoptosis rate,and the expression level of Bax in Ga-L and Ga-H groups were reduced,the levels of SOD,GSH,Bcl-2,p-AMPK/AMPK,SIRT1,and PGC-1αwere increased(P<0.05);Dorsomorphin attenuated the ameliorative effect of Ga-H on lung injury in hyperoxy-induced preterm rats.Conclusion Ga may inhibit inflammation,oxidative stress and apoptosis by activating the AMPK/SIRT1/PGC-1αpathway,and alleviate lung injury in premature rats induced by hyperoxia.